%0 Journal Article
%T Caenorhabditis elegans Protein Arginine Methyltransferase PRMT-5 Negatively Regulates DNA Damage-Induced Apoptosis
%A Mei Yang equal contributor
%A Jianwei Sun equal contributor
%A Xiaojuan Sun
%A Qinfang Shen
%A Zhiyang Gao
%A Chonglin Yang
%J PLOS Genetics
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pgen.1000514
%X Arginine methylation of histone and non-histone proteins is involved in transcription regulation and many other cellular processes. Nevertheless, whether such protein modification plays a regulatory role during apoptosis remains largely unknown. Here we report that the Caenorhabditis elegans homolog of mammalian type II arginine methyltransferase PRMT5 negatively regulates DNA damage-induced apoptosis. We show that inactivation of C. elegans prmt-5 leads to excessive apoptosis in germline following ionizing irradiation, which is due to a CEP-1/p53¨Cdependent up-regulation of the cell death initiator EGL-1. Moreover, we provide evidence that CBP-1, the worm ortholog of human p300/CBP, functions as a cofactor of CEP-1. PRMT-5 forms a complex with both CEP-1 and CBP-1 and can methylate the latter. Importantly, down-regulation of cbp-1 significantly suppresses DNA damage-induced egl-1 expression and apoptosis in prmt-5 mutant worms. These findings suggest that PRMT-5 likely represses CEP-1 transcriptional activity through CBP-1, which represents a novel regulatory mechanism of p53-dependent apoptosis.
%U http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000514